title: Genomic identification of potential targets unique to Candida albicans for the discovery of antifungal agents.
abstract: Despite of modern antifungal therapy, the mortality rates of invasive infection with human fungal pathogen Candida albicans are up to 40%. Studies suggest that drug resistance in the three most common species of human fungal pathogens viz., C. albicans, Aspergillus fumigatus (causing mortality rate up to 90%) and Cryptococcus neoformans (causing mortality rate up to 70%) is due to mutations in the target enzymes or high expression of drug transporter genes. Drug resistance in human fungal pathogens has led to an imperative need for the identification of new targets unique to fungal pathogens. In the present study, we have used a comparative genomics approach to find out potential target proteins unique to C. albicans, an opportunistic fungus responsible for severe infection in immune-compromised human. Interestingly, many target proteins of existing antifungal agents showed orthologs in human cells. To identify unique proteins, we have compared proteome of C. albicans [SC5314] i.e., 14,633 total proteins retrieved from the RefSeq database of NCBI, USA with proteome of human and non-pathogenic yeast Saccharomyces cerevisiae. Results showed that 4,568 proteins were identified unique to C. albicans as compared to those of human and later when these unique proteins were compared with S. cerevisiae proteome, finally 2,161 proteins were identified as unique proteins and after removing repeats total 1,618 unique proteins (42 functionally known, 1,566 hypothetical and 10 unknown) were selected as potential antifungal drug targets unique to C. albicans.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Tripathi
authors.forename: Suaib
authors.initials: S
authors.lastname: Luqman
authors.forename: Abha
authors.initials: A
authors.lastname: Meena
authors.affiliation: Department of Metabolic and Structural Biology, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O.-CIMAP, Kukrail Picnic Spot Road, Lucknow - 226 015 (U.P.), India. f.khan@cimap.res.in.
authors.forename: Feroz
authors.initials: F
authors.lastname: Khan
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D055808:Drug Discovery; D004352:Drug Resistance, Microbial; D005656:Fungal Proteins / Q000737:chemistry; D016681:Genome, Fungal; D006801:Humans; D008826:Microbial Sensitivity Tests; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D014157:Transcription Factors